JP6153863B2 - ワクチン接種方法 - Google Patents
ワクチン接種方法 Download PDFInfo
- Publication number
- JP6153863B2 JP6153863B2 JP2013504287A JP2013504287A JP6153863B2 JP 6153863 B2 JP6153863 B2 JP 6153863B2 JP 2013504287 A JP2013504287 A JP 2013504287A JP 2013504287 A JP2013504287 A JP 2013504287A JP 6153863 B2 JP6153863 B2 JP 6153863B2
- Authority
- JP
- Japan
- Prior art keywords
- skin
- antigen
- immune response
- enhancing
- inoculated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002255 vaccination Methods 0.000 title claims description 34
- 238000000034 method Methods 0.000 title description 51
- 239000000427 antigen Substances 0.000 claims description 149
- 108091007433 antigens Proteins 0.000 claims description 149
- 102000036639 antigens Human genes 0.000 claims description 149
- 210000003491 skin Anatomy 0.000 claims description 148
- 244000052769 pathogen Species 0.000 claims description 84
- 230000028993 immune response Effects 0.000 claims description 80
- 230000001717 pathogenic effect Effects 0.000 claims description 65
- 239000002671 adjuvant Substances 0.000 claims description 41
- 238000002360 preparation method Methods 0.000 claims description 39
- 230000002708 enhancing effect Effects 0.000 claims description 25
- 108010002616 Interleukin-5 Proteins 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 17
- 210000000434 stratum corneum Anatomy 0.000 claims description 17
- 238000002347 injection Methods 0.000 claims description 12
- 239000007924 injection Substances 0.000 claims description 12
- 241000700605 Viruses Species 0.000 claims description 10
- 239000002054 inoculum Substances 0.000 claims description 8
- 210000002966 serum Anatomy 0.000 claims description 7
- 102100037850 Interferon gamma Human genes 0.000 claims description 6
- 108010074328 Interferon-gamma Proteins 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 230000002458 infectious effect Effects 0.000 claims description 5
- 210000002510 keratinocyte Anatomy 0.000 claims description 5
- 241000894006 Bacteria Species 0.000 claims description 4
- 238000005411 Van der Waals force Methods 0.000 claims description 4
- 239000000853 adhesive Substances 0.000 claims description 4
- 230000001070 adhesive effect Effects 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 3
- 241000233866 Fungi Species 0.000 claims description 2
- 230000000890 antigenic effect Effects 0.000 claims description 2
- 244000045947 parasite Species 0.000 claims description 2
- 239000012678 infectious agent Substances 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 description 36
- 230000037452 priming Effects 0.000 description 32
- 238000002649 immunization Methods 0.000 description 27
- 230000003053 immunization Effects 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 22
- 238000009472 formulation Methods 0.000 description 16
- 108090000695 Cytokines Proteins 0.000 description 13
- 102000004127 Cytokines Human genes 0.000 description 13
- 230000036039 immunity Effects 0.000 description 13
- 230000004044 response Effects 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- 238000011081 inoculation Methods 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229960005486 vaccine Drugs 0.000 description 8
- 238000009169 immunotherapy Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 206010022000 influenza Diseases 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 230000003321 amplification Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000010255 intramuscular injection Methods 0.000 description 5
- 239000007927 intramuscular injection Substances 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 210000004989 spleen cell Anatomy 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000007933 dermal patch Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 210000003238 esophagus Anatomy 0.000 description 4
- 210000002865 immune cell Anatomy 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 208000005252 hepatitis A Diseases 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000010287 polarization Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000000230 African Trypanosomiasis Diseases 0.000 description 2
- 235000017060 Arachis glabrata Nutrition 0.000 description 2
- 241001553178 Arachis glabrata Species 0.000 description 2
- 235000010777 Arachis hypogaea Nutrition 0.000 description 2
- 235000018262 Arachis monticola Nutrition 0.000 description 2
- 102000009016 Cholera Toxin Human genes 0.000 description 2
- 108010049048 Cholera Toxin Proteins 0.000 description 2
- 241001115402 Ebolavirus Species 0.000 description 2
- 102100023688 Eotaxin Human genes 0.000 description 2
- 101710139422 Eotaxin Proteins 0.000 description 2
- 101001066288 Gallus gallus GATA-binding factor 3 Proteins 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000701806 Human papillomavirus Species 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 201000005702 Pertussis Diseases 0.000 description 2
- 206010037742 Rabies Diseases 0.000 description 2
- 241000702670 Rotavirus Species 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 206010043376 Tetanus Diseases 0.000 description 2
- 210000000447 Th1 cell Anatomy 0.000 description 2
- 210000004241 Th2 cell Anatomy 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 208000003152 Yellow Fever Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 208000029080 human African trypanosomiasis Diseases 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 210000001630 jejunum Anatomy 0.000 description 2
- 210000001821 langerhans cell Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 235000020232 peanut Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- -1 polypropylene Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 201000002612 sleeping sickness Diseases 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 201000003075 Crimean-Congo hemorrhagic fever Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 208000030820 Ebola disease Diseases 0.000 description 1
- 101710146739 Enterotoxin Proteins 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000893570 Hendra henipavirus Species 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 208000002979 Influenza in Birds Diseases 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 206010023927 Lassa fever Diseases 0.000 description 1
- 208000004023 Legionellosis Diseases 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 208000000932 Marburg Virus Disease Diseases 0.000 description 1
- 208000030156 Marburg disease Diseases 0.000 description 1
- 201000011013 Marburg hemorrhagic fever Diseases 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 206010027249 Meningitis meningococcal Diseases 0.000 description 1
- 201000010924 Meningococcal meningitis Diseases 0.000 description 1
- 229930191564 Monensin Natural products 0.000 description 1
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108010073443 Ribi adjuvant Proteins 0.000 description 1
- 208000000705 Rift Valley Fever Diseases 0.000 description 1
- 208000009714 Severe Dengue Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- UVJQIYZYQQKIAC-UHFFFAOYSA-N [amino(ethylsulfanyl)methylidene]-[4-(trifluoromethyl)phenyl]azanium;chloride Chemical compound Cl.CCSC(N)=NC1=CC=C(C(F)(F)F)C=C1 UVJQIYZYQQKIAC-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 208000020282 anthrax disease Diseases 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 206010064097 avian influenza Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- KQNZDYYTLMIZCT-KQPMLPITSA-N brefeldin A Chemical compound O[C@@H]1\C=C\C(=O)O[C@@H](C)CCC\C=C\[C@@H]2C[C@H](O)C[C@H]21 KQNZDYYTLMIZCT-KQPMLPITSA-N 0.000 description 1
- JUMGSHROWPPKFX-UHFFFAOYSA-N brefeldin-A Natural products CC1CCCC=CC2(C)CC(O)CC2(C)C(O)C=CC(=O)O1 JUMGSHROWPPKFX-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- XERAGTFKMJZSDI-UHFFFAOYSA-N ethene;ethenyl prop-2-enoate Chemical compound C=C.C=COC(=O)C=C XERAGTFKMJZSDI-UHFFFAOYSA-N 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000000799 fusogenic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 201000010284 hepatitis E Diseases 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960005358 monensin Drugs 0.000 description 1
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical class OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000017709 saponins Nutrition 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000029069 type 2 immune response Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 244000052613 viral pathogen Species 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/29—Hepatitis virus
- A61K39/292—Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/099—Bordetella
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2730/00—Reverse transcribing DNA viruses
- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
- C12N2730/10134—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Immunology (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Description
Mishra等, 2006は、局所的投与を介して抗原を輸送する新規の小胞状コンストラクト、融合性ベソソームを用いて経皮免疫化のシステムを提示している。しかしながら、この小胞性のシステムは、液体、非密封性システムであり、水を含ませた皮膚にアジュバントと共に抗原を適用する必要がある。
本発明の他の対象は、病原体に対して免疫化された哺乳動物における免疫反応を増強する方法であり、その方法は、病原体に特異的な抗原、好ましくは乾燥状態であり、アジュバントを利用しない製剤を接種対象の皮膚に適用することを含む。より好ましくは、その抗原製剤は、アジュバントを利用せず、接種対象の無処置領域に適用される。
本明細書で用いられるように、「従来型」投与又はワクチン接種は、非経口、経口又は経鼻の投与又はワクチン接種をいう。非経口投与は、注射(例えば、筋肉内、皮内、静脈内又は皮下)、穿刺、及び/又は経皮投与により行われ得る。好ましい非経口投与経路は注射である。
選択された病原体に対する接種対象への先の従来のワクチン接種、
選択された病原体に対する接種対象への先の従来の初回抗原刺激、及び/又は、
選択された病原体に対する接種対象への自然曝露、
により生じ得る。
[実施例]
実施例1:皮膚における追加免疫による免疫反応の増幅及びTH1指向化
A.材料及び方法
動物
大人のBALB/cマウスを、CharlesRiver Laboratories (フランス)から購入した。全ての試験は、動物飼育に関する欧州共同体の規則に従って行った。
B型肝炎ウィルスの表面抗原、すなわちHBsAgを用いた。
WO 2007/122226に記載されているようなViaskin(登録商標)デバイスを用いた。そのデバイスは、密封性であり、静電気的である。抗原は、乾燥状態で且つアジュバントを含まない状態で、静電気力により基材の表面に保持されている。
血液サンプルを免疫療法前及び免疫療法中に後眼窩の静脈叢から採取し、その血漿を更なる分析まで−30℃で保存した。
最後の血液のサンプリングの後、マウスを脊椎脱臼により殺し、無菌状態で脾臓を採取した。
細胞培養を24ウェルマイクロタイタープレート(2.106cells/well)でHBsAg(0〜50μg.ml−1)の存在下で行った。インビトロの刺激の72時間後、上清を回収し、IL−5及びIFNγの定量化を製造者の説明書に従って、CytoSetTMキット(BioSource International Europe,Belgium)を用いて行った。
細胞培養を製造者(BD, USA)の推奨に従って、ELISpotマイクロタイタープレート(R&D system, USA)でHBsAg(0〜50μg.ml−1)の存在下で行った。IL−5及びIFNγの定量化を、刺激の48時間後に行った。
初回抗原刺激:大人のBALB/Cマウス(7匹で2群)に対して2mgHBsAg/10μgAlOHで従来の免疫化(筋肉内注射)を行った。
血清の回収
グループ1「HBsAg/Alum」:2mgHBsAg/10μgAlOHでの追加免疫
グループ2「Viaskin(登録商標)/HBsAgパッチ」:100mgHBsAgを含むViaskinでの追加免疫。Viaskinを適用後48時間で外した。
血清の回収
グループ1:追加免疫なし
グループ2:100mgHBsAgを含むViaskinでの追加免疫
追加免疫1及び追加免疫2のためのパッチを2つの異なる方法で調製した:追加免疫1のためのパッチを凍結乾燥で調製し、追加免疫2のためのパッチを乾燥により調製した。しかしながら、2つの製剤において、パッチ上に抗原を粉末で付けた。
血清の回収
脾臓をT細胞反応の分析のために採取した。
エクスビボ:
脾臓細胞を、サイトカインの分泌を抑制するためのブレフェルディンA/モネンシンの添加前に、HBsAg(5mg/ml)の存在下又は非存在下で1時間培養した。
脾臓細胞を、72時間の分析の前に、抗原(5mg/ml及び20mg/ml)の存在下又は非存在下で培養した。
Graph Pad Software (SanDiego, USA)を統計分析のために用いた。データを、コントロールと処理したマウスとを比較する場合では分散分析(ANOVA)及びダネット検定を用いて分析し、全ての群を互いに比較する場合ではANOVA及びチューキー検定を用いて分析した。
抗HBsAg IgG1反応における本発明の皮膚への追加免疫の影響(図1)
提示した結果は、最初の皮膚パッチの適用によるIgG1の顕著な増幅を示す(図1のD49とD28との比較)。
提示した結果は、最初の皮膚パッチの適用によるIgG1の顕著な増幅を示す(図2のD49とD28との比較)。
図3に提示された結果は、IFNγ生成細胞の数がViaskinで追加免疫した場合とアジュバントを用いた筋肉内注射で追加免疫した場合とで類似しており、一方、IL−5生成細胞がViaskinで追加免疫した場合の方がより少ないことを示している。従って、HBsAg/AlOHでTh2誘導初回抗原刺激したにもかかわらず、Viaskinでの追加免疫は、(筋肉内注射による)HBsAg/AlOHの優先的なTh2反応に対して、釣り合っているTh1/Th2反応を誘導した。
72時間の時点で、Viaskinで追加免疫されたマウスのT細胞の上清には、(筋肉内注射による)HBsAg/AlOHでの追加免疫の場合と比較して、IFNγが顕著に高い濃度で存在し、IL−5が顕著に低い濃度で存在している。
72時間の時点で、Viaskinで追加免疫されたマウスの方が無処置のマウスよりも高いIL−5濃度を示した。
免疫化マウスからの脾臓細胞は、IFNγを自然に放出し、この放出は、Viaskinで追加免疫されたマウスにおいてより多くなる。
無処置のマウスと比較して、HBsAg/AlOHで追加免疫されたマウスでは、IFNγが顕著に高い濃度では検出されない。
本発明の皮膚への追加免疫は、HBsAg/AlOHで従来の初回抗原刺激されたマウスにおいて、抗HBsAgIgG1及びIgG2a反応を顕著に増大した。IgG1及びIgG2aレベルは、従来の追加免疫(アジュバントを用いた筋肉内注射)により得られたものと同等であった。皮膚への追加免疫は、IFNγを増大し、IL−5抗HBsAg反応を低減した。
A.材料及び方法
BALB/cマウスを、アジュバントとしてコレラ毒素と混合された落花生タンパク質抽出物(PPE)で胃内に6週間(1週間に1回)感作した。
無処置の皮膚への処理の後で、sIgEが低減し、sIgG2aが増大し、それぞれ0.036±0.01vs0.231±0.02μg/ml(EPITvsSham,p<0.05)及び2.86±0.78vs1.06±0.28μg/ml(p<0.05)であった。対照的に、テープストリップされた皮膚における免疫療法の後、sIgEは増大し、sIgG2aは変化せず、それぞれ0.383±0.08μg/ml(p<0.01vsSham)及び1.252±0.22μg/mlであった(図7A及び7Bを参照)。
得られた結果は、皮膚への免疫療法における、無処置の角質層の損傷度のレベルに依存して引き起こされる免疫学的反応のプロファイルを示す。
その結果は、十分な免疫反応が、密封性のデバイスを用いて適用されたアジュバントを使わない追加免疫を用いた皮膚に対する処置によって得られ得る、及び増幅され得る。その追加免疫は、抗原が無処置の皮膚に適用されるとき、TH1指向化を引き起こし、特に強い免疫反応を引き起こす。
Glenn, Scharton-Kerstenet al. 1999, 「Advances in vaccinedelivery: transcutaneous immunisation.」 Expert Opin InvestigDrugs 8(6): 797-805;
Kaiserlianand Etchart 1999 「Epicutaneous and transcutaneousimmunization using DNA or proteins.」 Eur J Dermatol 9(3): 169-76;
Partidos,Beignon et al. 2003, 「Delivering vaccines into the skin without needles and syringes.」 Expert Rev Vaccines 2(6):753-61 ;「Immunity under the skin: potential applicationfor topical delivery of vaccines.」 Vaccine 21(7-8): 776-80).
Shiver, JW et al., 2002, 「Replication-incompetent adenoviral vaccine vector elicits effectiveanti-immunodeficiency-virus immunity.」 Nature 415: 331-335.
Woodland DL et al., 2004, 「Jump-starting the immune system: prime-boosting comes of age.」 Trends Immunol. 25: 98-104.
Wu, L et al., 2005, 「Enhanced breadth of CD4 T-cell immunity by DNA prime and adenovirusboost immunization to human immunodeficiency virus Envand Gag immunogens.」 J Virol 79: 8024-8031.
McConnell et al., 2007,「Adenovirus-based prime-boost immunization for rapid Vaccinationagainst Anthrax.」 Molecular Therapy 15: 203-210.
Claims (12)
- 哺乳動物の接種対象の病原体に対する既存の免疫反応を増強するのに用いるための感染性病原体に特異的な抗原製剤であって、
アジュバントを用いず、接種対象の前処理が行われておらず、角質層の完全性を維持している無処置の皮膚領域に対して、角質層の完全性を変更することなく非穿孔性のパッチデバイスを用いて、各回5時間〜72時間の適用で少なくとも2回適用され、
前記既存の免疫反応は、前記接種対象への先の注射での前記病原体に対するワクチン接種により生じ、
前記増強される免疫反応は、Th1指向性である抗原製剤。 - 乾燥状態である請求項1に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 角質層の完全性を変更することなく、適用される部位における角質細胞を除去するための皮膚表面の水による洗浄後に、前記接種対象の皮膚に適用される、請求項1又は2に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 密封性のパッチデバイスを用いて前記接種対象の皮膚に適用される、請求項1〜3のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 前記密封性のパッチデバイスは、前記抗原が、接着剤が加えられずに静電気又はファンデルワールス力により結合された担体を含む、請求項4に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 前記接種対象の皮膚に3回の追加免疫として投与される、請求項1〜5のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 0.1μg〜10000μgの抗原量で24時間〜60時間皮膚に適用される第1の追加免疫、該第1の追加免疫後0.1μg〜10000μgの抗原量で24時間〜60時間皮膚に適用される第2の追加免疫、及び該第2の追加免疫後0.1μg〜10000μgの抗原量で24時間〜60時間皮膚に適用される第3の追加免疫として投与される、請求項1〜6のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 皮膚への追加免疫と先のワクチン接種とは、同一の抗原が用いられる、請求項1〜7のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 感染性病原体は、ウィルス、細菌、寄生生物又は真菌である、請求項1〜8のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 前記抗原は、ウィルス又は細菌の表面抗原である、請求項1〜9のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 追加免疫された哺乳動物の接種対象から抽出されたT細胞の上清におけるIFN−γ濃度の増大及びIL−5濃度の減少を引き起こす、請求項1〜10のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
- 追加免疫された哺乳動物の接種対象から得られた血清におけるIgE濃度の低減及びIgG2a濃度の減少を引き起こす、請求項1〜11のいずれか1項に記載の既存の免疫反応を増強するのに用いるための抗原製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP10305399.7 | 2010-04-16 | ||
EP10305399 | 2010-04-16 | ||
PCT/EP2011/055991 WO2011128430A1 (en) | 2010-04-16 | 2011-04-15 | Method of vaccination |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013525295A JP2013525295A (ja) | 2013-06-20 |
JP6153863B2 true JP6153863B2 (ja) | 2017-06-28 |
Family
ID=42668014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013504287A Active JP6153863B2 (ja) | 2010-04-16 | 2011-04-15 | ワクチン接種方法 |
Country Status (9)
Country | Link |
---|---|
US (2) | US20130039958A1 (ja) |
EP (1) | EP2547358B1 (ja) |
JP (1) | JP6153863B2 (ja) |
CN (2) | CN103096919A (ja) |
AU (1) | AU2011239941B2 (ja) |
CA (1) | CA2796004C (ja) |
ES (1) | ES2609839T3 (ja) |
IL (1) | IL222360B (ja) |
WO (1) | WO2011128430A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2924349B1 (fr) | 2007-12-03 | 2010-01-01 | Dbv Tech | Methode de desensibilitation aux allergenes |
FR2926466B1 (fr) * | 2008-01-23 | 2010-11-12 | Dbv Tech | Procede de fabrication de patchs par electrospray |
ES2534558T3 (es) | 2009-09-07 | 2015-04-24 | Dbv Technologies | Método de tratamiento de la esofagitis eosinofílica |
EP3820457A1 (en) | 2018-07-09 | 2021-05-19 | DBV Technologies | Optimized epicutaneous vaccination |
US20230355737A1 (en) | 2020-09-28 | 2023-11-09 | Dbv Technologies | Particle comprising an rsv-f protein for use in rsv vaccination |
AU2021456003A1 (en) | 2021-07-16 | 2024-02-15 | Dbv Technologies | Immunotherapeutic method for increasing cashew tolerance in a subject |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6797276B1 (en) | 1996-11-14 | 2004-09-28 | The United States Of America As Represented By The Secretary Of The Army | Use of penetration enhancers and barrier disruption agents to enhance the transcutaneous immune response |
FR2822049B1 (fr) | 2001-03-13 | 2003-08-01 | Dbv Medica 1 | Patch destine notamment a depister l'etat de sensibilisation d'un sujet a un allergene, procede de fabrication et utilisation |
US7635488B2 (en) * | 2001-03-13 | 2009-12-22 | Dbv Technologies | Patches and uses thereof |
EP1545605B8 (en) * | 2002-10-02 | 2010-05-26 | Nordic Vaccine A/S | Composition for vaccination |
FR2924350B1 (fr) * | 2007-12-03 | 2010-08-13 | Dbv Tech | Procede et compositions pour la vaccination par voie cutanee |
-
2011
- 2011-04-15 CN CN2011800278469A patent/CN103096919A/zh active Pending
- 2011-04-15 JP JP2013504287A patent/JP6153863B2/ja active Active
- 2011-04-15 EP EP11714559.9A patent/EP2547358B1/en active Active
- 2011-04-15 ES ES11714559.9T patent/ES2609839T3/es active Active
- 2011-04-15 AU AU2011239941A patent/AU2011239941B2/en active Active
- 2011-04-15 WO PCT/EP2011/055991 patent/WO2011128430A1/en active Application Filing
- 2011-04-15 CA CA2796004A patent/CA2796004C/en active Active
- 2011-04-15 CN CN201710561017.8A patent/CN107441483A/zh active Pending
-
2012
- 2012-10-11 IL IL222360A patent/IL222360B/en active IP Right Grant
- 2012-10-12 US US13/651,143 patent/US20130039958A1/en not_active Abandoned
-
2018
- 2018-11-02 US US16/179,851 patent/US20190070286A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU2011239941A1 (en) | 2012-11-08 |
CA2796004A1 (en) | 2011-10-20 |
IL222360B (en) | 2018-06-28 |
WO2011128430A1 (en) | 2011-10-20 |
EP2547358B1 (en) | 2016-11-02 |
CA2796004C (en) | 2020-09-22 |
US20190070286A1 (en) | 2019-03-07 |
IL222360A0 (en) | 2012-12-31 |
JP2013525295A (ja) | 2013-06-20 |
EP2547358A1 (en) | 2013-01-23 |
CN107441483A (zh) | 2017-12-08 |
ES2609839T3 (es) | 2017-04-24 |
AU2011239941B2 (en) | 2015-07-16 |
CN103096919A (zh) | 2013-05-08 |
US20130039958A1 (en) | 2013-02-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20190070286A1 (en) | Method of vaccination | |
Cui | DNA vaccine | |
Ellis | New technologies for making vaccines | |
Ellis | Technologies for the design, discovery, formulation and administration of vaccines | |
Plotkin | Six revolutions in vaccinology | |
Nguyen et al. | Skin immunization with third-generation hepatitis B surface antigen using microneedles | |
Schulze et al. | New horizons in the development of novel needle-free immunization strategies to increase vaccination efficacy | |
Depelsenaire et al. | Introduction to vaccines and vaccination | |
Osorio et al. | Immune responses to hepatitis B surface antigen following epidermal powder immunization | |
JP5186678B2 (ja) | 経皮抗原投与のための抗原キット | |
US11938178B2 (en) | Optimized epicutaneous vaccination | |
Glenn et al. | Transcutaneous immunization | |
Seid Jr et al. | Advances in transcutaneous vaccine delivery | |
US20140322272A1 (en) | Vaccine | |
US20120231044A1 (en) | Vaccine formulation of mannose coated peptide particles | |
Kasi | 33 Adult Vaccination | |
Le Grand et al. | Recombinant Vaccines: Development, Production, and Application | |
Seid Jr et al. | Transcutaneous immunization via vaccine patch delivery system | |
RU2362586C2 (ru) | Фармацевтические композиции для терапевтического применения | |
US20050129712A1 (en) | Combined dna/protein vaccine compositions | |
Kasi | Future Vaccines | |
CN113876941A (zh) | 一种新的快速高效低价的人工合成疫苗的设计和应用 | |
Kraan | Alternative delivery of polio vaccines | |
JP2010284176A (ja) | 製剤、当該製剤を用いたワクチンの投与方法及びイオントフォレーシス装置 | |
WO2014044690A1 (en) | Improved vaccines |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140320 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150317 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150615 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150915 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160115 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160225 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160318 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20160428 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170324 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170531 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6153863 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |